LSDs are disorders caused due to some enzymes deficiencies in the body which are genetically determined and most of them are autosomal recessive. Some of them may be comparatively more commonly seen and some of them may be extremely rare and hence, their diagnosis is very challenging. Lack of awareness about these disorders their mimicking symptoms and lack of diagnostic facilities are some of the major challenges faced.Shahid Akhter | ETHealthWorld | Updated: September 08, 2017, 09:17 IST

In an interview with ETHealthworld,Dr. Madhulika Kabra, Professor Division of Genetics, Department of Pediatrics, AIIMS, New Delhi, talks about the rare disease scenario in India. Edited excerpts:

What exactly are rare diseases? How are they defined?There is no global definition of rare diseases, different countries define rare disease differently based on their resources and whatever epidemiological data is existing in that particular country. A disease or disorder is defined as rare in Europe when it affects fewer than 1 in 2000. A disease or disorder is defined as rare in the USA when it affects fewer than 200,000 Americans at any given time and so on. India doesn’t have any epidemiological data on rare diseases to define rare diseases presently.

World over almost seven thousand rare diseases have been described. There are huge number of rare diseases if you go to the websites and it is very difficult to even list all of them. But then some of which are seen in clinical practice not only in tertiary care centers but also in specialized centers like pediatric, neurology and hematological practice include inborn errors of metabolism like Lysosomal Storage Disorders and some small molecule disorders like organic acidemias, urea cycle disorders, hematological disorders, skeletal dysplasias, cystic fibrosis, immune deficiency disorders, neuromuscular disorders etc.

Tell us something about the global scenario and the incidence of rare diseases in India.The prevalence of some of the rare disorders is available from certain countries, where they have epidemiological data available, community based or hospital based, but we do not have any such data available from India. A recent initiative which has been taken by the Indian Council of Medical Research (ICMR) is to come up with the rare disease registry, choosing some of the disorders to begin with and collect hospital based data as of now. The focus is on treatable disorders to begin with.

What are the challenges that you face in the diagnosis of rare diseases?In rare diseases, the numbers are huge, that is one. Some of them may be comparatively more commonly seen while some may be extremely rare which one may see once in a lifetime. Some of the disorders which are seen in clinical practice, the diagnosis may be missed for few reasons. One could be that the awareness is not there and some of the rare diseases are mimickers. They may mimic some of the other common disorders which are seen in clinical practice. For example Gaucher’s disease presents with liver and spleen enlargement, anemia and thrombocytopenia, which can be manifestations of many common disorders as well. Once the patient comes, we always think of a commoner diagnosis first.

The other issue is that even if the diagnosis is thought of or is kept as a differential diagnosis the facilities for diagnosis may not be available everywhere. In the last few years these facilities have really improved and many labs are offering these tests and there are facilities for easy and safe transport of samples as well. Cost of the tests may also be an issue for a significant proportion of families.

Is there a need for improving the diagnostic facilities for LSDs? What are the steps that can be taken for timely diagnosis?Yes there is a definite need. If you are talking about Lysosomal Storage Disorders (LSDs) which are relatively common and seen in clinical practice, the clinicians who are likely to see these disorders should know that when they should think of LSDs. So, the steps could be:• Medical education is very important and that is going on in a big way and which is probably the reason that the diagnostic capabilities have really improved over time. Though this needs further dissemination.• Although the facilities are available in some government and many private setups, these are limited to bigger cities.• There is a need to have improvement on this, more labs should be available and the existing labs should be strengthened also. It is important to deal with quality assurance issues where ever these tests are being offered.

What kind of treatments are currently available for LSDs? How can we ensure that they are accessible to maximum number of patients?There is a plethora of Lysosomal Storage Disorders. Lysosomal Storage Disorders are inherited disorders and most of them are autosomal recessive which means that both the parents are carriers and there is a 25% chance that the baby will have the disease in each pregnancy. As the problem is with the enzyme which metabolizes certain substrates in the cells, waste products accumulate in the cells, and different organ systemsof the body get affected. This leads to various manifestations which include central nervous system, hematological system, skeletal system eyes etc.

In therapy, first is the Enzyme Replacement Therapy (ERT) which is available for seven of these disorders as of now. This is intravenous therapy which needs to be given every week or two weeks. The cost of the enzyme is very high presently. For few disorders, oral therapy is also available which is also very expensive and can be given to children over 16 years only. ERT is the preferred mode of therapy and has been found to be effective and safe for all disorders though long term experience is available with few disorders. The main disadvantage of ERT is that the enzyme does not reach the brain and does not significantly improve skeletal and cardiac involvement.

The experience is most for Gaucher’s disease for which the treatment is most rewarding. Another mode of therapy is Hematopoietic stem cells transplantation (HSCT). Before ERT was available for these disorders, the main stay of therapy was HSCT. There are various problems in that because we need to have a matched donor and there can be morbidity because of immune suppression. Importantly, experience with HSCT is limited.

Talking of treatment accessibility, this needs a thorough brain storming at all levels which includes the treating physicians, policy makers and the parents. The funding is a major issue due to exorbitant cost and lifelong therapy if we are talking of ERT. As treatment is now available for a small number of disorders, there should be transparent uniform guidelines for prioritization of disorders based on the cost of treatment involved and evidence based response and outcomes. Various funding options should be explored and deliberated at the government level.

With immense pride “India Live” celebrated its 10th national conference in Mumbai from 28th February to 3rd March 2019. The conference turned out to be a gold mine of information, with emphasis on academics, education and exchange of knowledge with leaders in interventional cardiology from both India and abroad.